NM_007110.5:c.-25+2253A>C

Variant names:

• chr14-20411152-T-G
• rs2678685
• NM_007110.5:c.-25+2253A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007110.5(TEP1):​c.-25+2253A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,936 control chromosomes in the GnomAD database, including 22,257 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22257 hom., cov: 31)
• Consequence: TEP1 NM_007110.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 5 publications found

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	NM_007110.5	MANE Select	c.-25+2253A>C		intron	N/A	NP_009041.2
	TEP1	NM_001319035.2		c.-25+2253A>C		intron	N/A	NP_001305964.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEP1	ENST00000262715.10	TSL:1 MANE Select	c.-25+2253A>C		intron	N/A	ENSP00000262715.5
	TEP1	ENST00000556935.5	TSL:1	c.-25+2253A>C		intron	N/A	ENSP00000452574.1
	TEP1	ENST00000555727.5	TSL:1	n.-25+2253A>C		intron	N/A	ENSP00000451634.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81736 AN: 151818 Hom.: 22237 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81789 AN: 151936 Hom.: 22257 Cov.: 31 AF XY: 0.536 AC XY: 39832 AN XY: 74254

African (AFR) AF: 0.614 AC: 25447 AN: 41424

American (AMR) AF: 0.514 AC: 7844 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1819 AN: 3470

East Asian (EAS) AF: 0.594 AC: 3072 AN: 5174

South Asian (SAS) AF: 0.403 AC: 1939 AN: 4810

European-Finnish (FIN) AF: 0.547 AC: 5762 AN: 10542

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34205 AN: 67942

Other (OTH) AF: 0.538 AC: 1135 AN: 2110

Alfa AF: 0.518 Hom.: 35989

Bravo AF: 0.546

Asia WGS AF: 0.505 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2678685; hg19: chr14-20879311;